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The effect of absolute lymphocyte count recovery kinetics on survival after autologous stem cell transplantation for non-Hodgkin's lymphoma.

Absolute lymphocyte count (ALC) >or=500 cells/microl at day 15 after autologous stem cell transplantation (ASCT) is a powerful independent, prognostic indicator for survival in multiple hematological malignancies. A limitation in these studies was the selection of a single time point (day 15 post-ASCT) as the only discriminator of clinical outcome in relation to ALC recovery. We hypothesized there is a continuous and not discrete relationship between ALC recovery and clinical outcome post-ASCT in NHL. Therefore, we analyzed 274 consecutive patients who underwent ASCT for NHL between 1987 and 2001. The primary end point was to assess the impact of the kinetics of post-ASCT lymphocyte recovery>or=500 cells/microl (K-ALC) on overall survival (OS) and progression-free survival (PFS). K-ALC was a predictor of OS and PFS when the Cox proportional hazards model was used with K-ALC entered as a continuous variable (p<0.0001). Multivariate analysis demonstrated K-ALC recovery post-ASCT to be an independent prognostic indicator for OS and PFS. These data support our hypothesis that the K-ALC post-ASCT is associated with clinical outcome in NHL.

Adolescent↗

Differentiating large cell lymphoma from indolent small B-cell lymphoma in fine needle aspirates using p53, PCNA and transformed lymphocyte count.

OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as adjunctive tests to differentiate indolent small B-cell lymphoma from large cell lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The percentage of TLCs was determined on the Papanicolaou smear. The percentage and intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block sections. These results were compared and correlated with the final diagnoses based on available morphology, flow cytometry and clinical history. RESULTS: There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes. Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2 follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas, 2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53 nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53), followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas (7%); however, TLC was the best parameter for differentiating large cell lymphoma from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone or in combination. Significant overlap between categories limits usefulness of these immunocytochemical stains for differentiating these entities.

Biopsy, Needle↗

Effect of caffeine ingestion on lymphocyte counts and subset activation in vivo following strenuous cycling.

Caffeine ingestion is associated with increases in the concentration of plasma epinephrine and epinephrine is associated with alterations in immune cell trafficking and function following intensive exercise. Therefore, the purpose of this study was to investigate the effect of caffeine ingestion on plasma epinephrine concentration, lymphocyte counts and subset activation in vivo, as measured by the expression the CD69 surface antigen, before and after intensive cycling. On two occasions, following an overnight fast and 60 h abstention from caffeine containing foods and drinks, eight endurance trained males cycled for 90 min at 70% O(2 max) 60 min after ingesting caffeine (6 mg kg(-1 )body mass; CAF) or placebo (PLA). Venous blood samples were collected at pre-treatment, pre-exercise, post-exercise and 1 h post-exercise. Plasma epinephrine concentrations were significantly higher in CAF compared with PLA at pre-exercise [0.28 (0.05) nmol l(-1) versus 0.08 (0.03) nmol l(-1), P<0.01; mean (SE)] and immediately post-exercise [1.02 (0.16) nmol l(-1) versuss 0.60 (0.13) nmol l(-1), P<0.01]. Compared with pre-treatment, numbers of CD4(+) and CD8(+) cells decreased by 54% and 55%, respectively, in CAF at 1 h post-exercise (both P<0.01) but did not significantly differ in PLA. Compared with PLA, in CAF the percentage of CD4(+)CD69(+) cells was 5-fold higher at post-exercise (P<0.05) and 5.5-fold higher at 1 h post-exercise (P=0.01). Compared with PLA, in CAF the percentage of CD8(+)CD69(+) cells was 2-fold higher at pre-exercise (P<0.05) and 1.7-fold higher at post-exercise (P<0.05). These findings suggest that caffeine ingestion is associated with alterations in lymphocyte subset trafficking and expression of CD69 in vivo following prolonged, intensive exercise.

Administration, Oral↗

Use of beta 2-microglobulin level and CD4 lymphocyte count to predict development of acquired immunodeficiency syndrome in persons with human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2M) levels were measured by radioimmunoassay in 962 unmarried men recruited by probability sampling from areas in San Francisco, Calif, most severely affected by the epidemic of acquired immunodeficiency syndrome (AIDS). From July 1984 to December 1987, 65 incident AIDS cases occurred in 388 homosexual/bisexual men infected by the human immunodeficiency virus (HIV) at the time of recruitment. The mean level of beta 2M in uninfected individuals at entry was 170 nmol/L. In HIV-seropositive patients who had not developed AIDS, the mean beta 2M level was 254 nmol/L, and in those who had developed AIDS, the beta 2M level was 347 nmol/L. After 36 months of follow-up, 34% of individuals with beta 2M levels greater than 322 nmol/L at entry developed AIDS, 21% of individuals with levels between 246 and 322 nmol/L developed AIDS, while only 7.3% of those with levels below 246 nmol/L developed AIDS. The beta 2M level predicted the development of AIDS independently of the CD4 lymphocyte count in HIV-seropositive individuals. Thus, 65.5% of HIV-seropositive individuals with beta 2M levels above 322 nmol/L and CD4 lymphocyte counts of below 500/microL developed AIDS in 3 years. This represents an 18.4-fold increased relative hazard at 3 years over individuals with beta 2M and CD4 cell counts within the reference range for uninfected individuals. A nomogram is provided that allows the easy calculation of the probability of an HIV-infected person developing AIDS in 36 months depending on prevalent levels of CD4 lymphocytes and serum beta 2M.

Acquired Immunodeficiency Syndrome↗

Within-subject variation in CD4 lymphocyte count in asymptomatic human immunodeficiency virus infection: implications for patient monitoring.

Changes in CD4 lymphocyte counts are widely used in monitoring human immunodeficiency virus (HIV)-infected patients for disease progression. However, random fluctuations may obscure clinically significant changes. CD4 cell counts from 1020 untreated subjects with asymptomatic HIV infection monitored by standardized methods for up to 2 years were assessed. The within-subject coefficient of variation averaged 25% but was higher in subjects with lower counts; in 6% of subjects the count was half or double the one obtained 8 weeks before. Proportionate rates of decline, which had negligible correlation with the baseline count, averaged 14.3%/year but varied considerably between subjects: An estimated 29% had increasing trends. Declines were greater in HIV p24-positive subjects and those with higher lymphocyte percentages or lower platelet counts or hemoglobin levels. With such high variation, changes between single counts should be interpreted cautiously. Using multiple counts and other markers may provide more precise assessment of immune status.

Acquired Immunodeficiency Syndrome↗

Gut intraepithelial lymphocyte counts in neonates, infants and children.

Intraepithelial lymphocyte (IEL) counts were histologically assessed in the jejunum, ileum and appendix of 39 neonates (0-28 days), 32 infants (1-9 months) and 13 children (1-9 years). Small intestinal mucosa samples were obtained from 73 autopsies, and from 8 surgical and 3 aspirative biopsies. IEL counts of specimens from the jejunum, ileum and appendix gave similar results in the same patient. The number of IEL counts was significantly lower in neonates for all three segments. The difference between infants and children was more marked in the jejunum than in the ileum, although this was not significant. In the appendix, there was no difference between the different age groups. Our results indicate that postnatal expansion of IEL occurs homogeneously along the gut after the neonatal period.

Appendix↗

The predictive value of T-lymphocyte counts in breast cancer patients treated by endocrine manipulation.

Endocrine manipulation has a valuable role in the management of advanced breast cancer. However, it is only effective in some cases and at least 12 weeks is required before efficacy can be ascertained. In an attempt to achieve earlier assessment of response, changes in lymphocyte counts have been studied in patients receiving endocrine therapy. Absolute lymphocytes were not significantly changed by 6 weeks in any patients but there was a significant increase (P less than 0.05) in absolute T counts by 6 weeks in patients who achieved partial remission when compared with those whose disease continued to progress. Percentage T counts increased significantly from pretreatment values (P less than 0.002) in patients in whom disease progression was stopped by endocrine manipulation and this rise was maintained during clinical benefit. Fall in percentage T counts to pretreatment values predated objective evidence of recurrence by as much as 2 months. There was no increase in percentage T counts in patients in whom disease progression continued despite treatment, indicating that the rise in percentage T counts is a secondary phenomenon to tumour response. T-lymphocyte counts may permit earlier evaluation of the patient during treatment, allowing earlier selection of alternative treatment modalities.

Adrenalectomy↗

The peripheral lymphocyte count predicts graft survival in DA to Lewis heterotopic heart transplantation treated with FTY720 and SDZ RAD.

OBJECTIVE: The new immunomodulator 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride (FTY720) lowers the peripheral lymphocyte count (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid organs. This effect is dose-dependent at low (up to 0.1 mg/kg per day) doses in rats. We investigated the correlation between PLC and the later rejection, when FTY720 was combined with RAD. METHODS: Heterotopic cardiac grafting was performed using the DA-Lewis strain combination. FTY720 and RAD were administered as single daily doses by gavage alone and in combination starting 3 days before to 28 days after transplantation. Graft survival was monitored daily by palpation. PLC was determined at 1 and 4 weeks, body weight (BW) weekly. Histologic evaluation of grafted hearts was performed after rejection. MAIN FINDINGS: FTY720 at doses of 0.03, 0.1 and 0.3 mg/kg per day prolonged graft survival dose-dependently from 6 (placebo) to 7, 9.5 and 15 days median survival time (MST). RAD at doses of 0.3, 1 and 3 mg/kg per day delayed rejection to 8.5, 18 and 37.5 days MST. Very small FTY720 doses added to the lower RAD doses were effective in maintaining grafts throughout the treatment period and with normal weight gain, as opposed to regimens with 1 mg/kg or more per day RAD, which resulted in delayed weight gain. FTY720 lowered the PLC significantly and dose-dependently. The PLC correlated well with graft survival [Spearman rank correlation (n = 30, rs = -0.75)]. CONCLUSIONS: Fully effective FTY720 + RAD combination regimens caused no side effects with respect to the rats' general well-being or weight gain and were better tolerated than equiactive RAD monotherapy, suggesting a broader therapeutic window for the combinations. Under the experimental conditions, the PLC decrease showed an interesting correlation with the anti-rejection effects in these two-drug regimens. Thus, in rats the PLC is helpful for monitoring the biological activity of FTY720 at low doses (< 0.1 mg/kg per day), i.e. in the range of the steep part of its dose-response relationship.

Animals↗

Prognosis in low grade non-Hodgkin's lymphoma: relevance of the number of sites involved, absolute lymphocyte count and serum immunoglobulin level.

Eighty-eight patients with low grade non-Hodgkin's lymphoma were followed for a median period of 63 months. Sixty-eight per cent of the group were centrocytic/centroblastic B cell lymphomas by the updated Kiel classification. Fifty-one (58 per cent) of the patients were stage IV by the Ann Arbor classification. In 18 of these patients the bone marrow was the only site of extranodal involvement. Univariate survival analysis showed that the sum of involved sites was more discriminatory than Ann Arbor stage. Analysis by site of involvement showed that the liver and other intraabdominal sites were associated with worse survival than involvement of peripheral lymph nodes. Bone marrow and spleen involvement were not significantly associated with short survival. Increasing age at presentation was strongly associated with shorter survival and was also inversely correlated with serum albumin. Both low absolute lymphocyte count (< 1.0 x 10(9)/l), low serum IgG level (< 10 g/l) and low total immunoglobulins on presentation were significantly associated with short survival. Multivariate analysis showed that age, serum albumin and number of involved sites gave the best survival prediction. The sum of involved sites, immunoglobulin level and absolute lymphocyte count may be useful objective markers of prognosis in low-grade non-Hodgkin's lymphoma.

Adolescent↗

A series of bed exercises to improve lymphocyte count in allogeneic bone marrow transplantation patients.

The purpose of this study was to investigate the effect of a series of bed exercises on lymphocyte and T-cell subsets in allogeneic bone marrow transplantation patients during hospitalization. Thirty-five patients were randomly assigned, with 18 assigned to an exercise group and 17 to a control group. The bed exercise intervention was applied by a nurse to the exercise group for 30 min every day for 6 weeks. Patients in the exercise group had a mean increase of 40.9 lymphocyte cells/microL and patients in the control group had a mean decrease of 640.7 lymphocyte cells/microL. There were no significant differences in the percentage of cluster of differentiation (CD)3+, CD4+ and CD8+, and CD4+/CD8+ ratio between the two groups. These findings indicate that bed exercise could be an effective nursing intervention with patients undergoing bone marrow transplantation by increasing the lymphocyte count during hospitalization.

Adult↗

Peripheral B- and T-lymphocyte counts in patients with sarcoma and breast carcinoma.

Peripheral B- and T-lymphocyte counts were studied in 50 patients before they received any therapy for their conditions: 16 had carcinoma of the breast; 8 soft tissue sarcoma; and 26, benign disease. Among 11 males, the six patients with advanced soft tissue sarcoma had significantly lower percentages of T lymphocytes than five patients with benign conditions. And six female patients with advanced breast cancers had significantly higher numbers of B lymphocytes than the 10 patients with early breast malignancies. Pertinent reports in the literature were reviewed and discussed. Presently, the clinical and prognostic values of quantitative study of T and B lymphocytes remain to be defined.

Adolescent↗

Peripheral blood CD4 + T-lymphocyte counts during Pneumocystis carinii pneumonia in immunocompromised patients without HIV infection.

STUDY OBJECTIVES: To assess the potential use of peripheral blood CD4 + T-lymphocyte counts (CD4 + counts) as a clinically useful biological marker to identify specific immunocompromised patients (without HIV infection) at high risk for Pneumocystis carinii pneumonia (PCP). DESIGN: Prospective observational study. SETTING: Three hundred seventy-five-bed tertiary-care urban referral teaching hospital, and 250-bed community-based referral hospital. PATIENTS: One hundred seventy-one consecutive confirmed HIV-seronegative hospitalized and ambulatory adults, including 22 patients with active PCP, 8 patients with bacterial pneumonia, 24 persons in two groups considered at high clinical risk, 38 persons in two groups considered at low or undefined risk, and 79 persons in four groups considered not at risk for PCP (including healthy individuals). MEASUREMENTS AND RESULTS: Compared to counts in healthy individuals, median CD4 + counts were significantly decreased in patients with active PCP (61 cells/microL vs 832 cells/microL; p = 0.001) where 91% of patients had a CD4 + count < 300 cells/microL at the time of PCP diagnosis. Median CD4 + counts were also reduced in the high clinical risk groups of recent organ transplant recipients (117 cells/microL; p = 0.007), 64% with < 300 cells/microL, and patients receiving chemotherapy (221 cells/microL; p<0.01), 80% with < 300 cells/microL. For the low or undefined clinical risk groups, the median CD4 + counts were not significantly reduced, although 39 to 46% of individuals receiving long-term corticosteroid therapy (alone or in combination with other agents) had CD4 + counts < 300 cells/microL. Median CD4 + counts in individuals considered not at risk for PCP were similar to those in healthy subjects. Compared to counts in patients with active PCP, median CD4 + counts were significantly higher in bacterial pneumonia patients (486 cells/microL; p<0.05), but similar to those in healthy subjects. CONCLUSIONS: These data suggest that for immunosuppressed persons without HIV infection (especially in low or undefined PCP risk groups), CD4 + counts may be a useful clinical marker to identify specific individuals at particularly high clinical risk for PCP and may help to guide chemoprophylaxis.

Adult↗

Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications.

OBJECTIVES: Research suggests that individuals with posttraumatic stress disorder (PTSD) are more likely to develop medical conditions and other stress-related psychiatric disorders. Given these findings and others suggesting that PTSD victims may have altered neuroendocrine and immune systems, the hypothesis that Vietnam veterans with PTSD have abnormally high leukocyte and lymphocyte counts was tested. METHODS: The leukocyte and lymphocyte status of male Vietnam "theater" veterans with current partial posttraumatic stress (N = 286), anxiety (N = 274), and depression disorders (N = 192) were compared with those of Vietnam veterans without these disorders 20 years after military service (N = 2190), controlling for intelligence, race, age, income, education, type of enlistment, Vietnam volunteer status, region of birth, cigarette smoking, illicit drug use, body mass index, and alcohol consumption. Abnormal values were defined using standard laboratory reference ranges. Adjusted mean differences also were compared. RESULTS: Based on the results of two-tailed tests, PTSD-positive veterans are more likely to have adjusted leukocyte (OR = 1.83, p = .04) and T-cell (OR = 1.82, p = .045) counts above the normal range and higher mean adjusted leukocyte (p = .042), lymphocyte (p = .01), T-cell (p = .008), and CD4 cell (p = .027) counts. Those with anxiety disorders have adjusted lymphocyte (OR = 1.68, p = .048) and T-cell (OR = 2.06, p = .011) counts above range. They also have test results indicating reactive delayed cutaneous hypersensitivity (OR = 1.77, p = .006), which suggests the presence of highly sensitized T-cell lymphocytes. Finally, depressed veterans are less likely to have B-cell counts above the reference range (OR = 0.55, p = .006). Results of one-tailed tests further suggest that PTSD-positive men also have abnormally high CD4 and CD8 T-cell lymphocyte counts as well (p < .05). CONCLUSIONS: Our findings suggest that chronic, primarily combat-related PTSD is associated with clinically elevated leukocyte and total T-cell counts. Those with current anxiety also have some of these abnormalities in addition to highly sensitized T-cell lymphocytes. Additional research is needed to specify the mechanisms involved here and to investigate the health risks associated with these findings.

Adult↗

[Oral manifestations, CD4+ T-lymphocytes count and viral load in Brazilian and North-American HIV-infected children].

Oral manifestations related to HIV infection were evaluated in 184 children of both genders, aging 0-13 years. The oral exams were carried out at the Ambulatory of Pediatric AIDS, São Lucas Hospital and at the Clinics Hospital, both in Porto Alegre, RS, Brazil, and at the University Hospital and School of Dentistry, State University of New York, Stony Brook, NY, USA, from January 1999 to May 2000. A high prevalence of oral manifestations was observed both in Brazilian (72.73%) and American (53.66%) children. The most frequent manifestations were cervical lymphadenopathy, swelling of the parotids, erythematous candidiasis, petechia, gingivitis, xerostomia and angular cheilitis. Children with oral manifestations had almost normal counts of CD4+ T lymphocytes and high viral load.

Adolescent↗

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). METHODS: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. RESULTS: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

CD4 Lymphocyte Count↗

Change in T-lymphocyte count after initiation of highly active antiretroviral therapy in HIV-infected patients with history of Mycobacterium avium complex infection.

OBJECTIVE: To compare changes in CD4+, CD8+ and total lymphocyte counts after initiation of highly active antiretroviral therapy (HAART) between HIV-infected patients with and without a recent history of Mycobacterium avium complex (MAC) infection. METHOD: Matched exposed-non-exposed retrospective cohort study. RESULTS: Fifty-one patients with a recent history of MAC infection (MAC+) started a combination of at least three antiretroviral drugs. They were individually matched to 145 patients without any history of MAC infection (MAC-) according to CD4+ T-cell count (+/- 30 cells/mm3), previous experience of antiretroviral treatment, AIDS clinical stage at the time of HAART initiation (baseline), age (+/- 10 years) and gender. MAC+ and MAC- patients presented comparable median levels of total lymphocytes (488 vs 688/mm3, P=0.09), CD4+ (11 vs 16/mm3, P=0.15), CD8+ count (359 vs 386/mm3, P=0.39) and plasma HIV RNA (5.3 vs 5.1 log10 copies/ml, P=0.22) at baseline. After 6 months on HAART, the median increase of CD4+ T-cell count was 28 cells/mm3 (interquartile range [IQR]: 1-63) in MAC+ and 72 cells/mm3 (IQR: 34-120) in MAC- patients (P<0.0001), whereas the percentage of CD4+ T cells was not significantly different between the two groups (P=0.13). Comparable differences were observed for total lymphocytes and CD8+ T cells (P<0.001). The 6 months decline of plasma HIV RNA was not significantly different according to MAC exposure (-1.6 in MAC+ vs -1.8 log10 copies/ml in MAC- patients, P=0.65). Results were confirmed after adjustment for other characteristics than the matching variables and after taking into account potential informative bias due to unbalanced number of deaths between the two groups. CONCLUSION: MAC infection at the time of HAART initiation is an important deleterious factor for immune reconstitution. A better understanding of the underlying mechanism and an evaluation of additional treatment strategies are necessary to help immune restoration in such circumstances.

AIDS-Related Opportunistic Infections↗

Precision and accuracy of absolute lymphocyte counts.

A critique of leukocyte counting using automated hematology instruments is presented. Important preanalytical variables include the anticoagulant and specimen assay delays. The precision of counts is directly related to the number of leukocytes counted. Criteria for the selection of an acceptable hematology laboratory for lymphocyte counts for CD4 determinations are presented.

Acquired Immunodeficiency Syndrome↗

Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection.

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups.

Adult↗